Key Findings:
The LDL receptor-deficient mouse (LDLrKO) is a model that mimics the human atherosclerotic condition. ALA in flaxseed is believed to be responsible for the positive effects noted on this model in this study that fed milled flaxseed. Specifically, reductions were found in the infiltration of macrophages into the subendothelial space and in inflammatory and proliferative states of atherosclerotic lesions. The anti atherogenic effects described in this study may also be associated with the low omega 6 to 3 fatty acid ratio in the plasma of the flaxseed-fed groups. The study shows that dietary flaxseed can inhibit the atherogenic effects of a high-cholesterol diet in the LDLrKO mouse possibly by reducing cholesterol levels and, at a cellular level, by inhibiting cell proliferation and inflammation.
ABSTRACT:
Dietary flaxseed has been shown to have potent antiatherogenic effects in rabbits. The purpose of the present study was to investigate the antiatherogenic capacity of flaxseed in an animal model that more closely represents the human atherosclerotic condition, the LDL receptor-deficient mouse (LDLrKO), and to identify the cellular mechanisms for these effects. LDLrKO mice were administered a regular diet (RG), a 10% flaxseed-supplemented diet (FX), or an atherogenic diet containing 2% cholesterol alone (CH) or supplemented with 10% flaxseed (CF), 5% flaxseed (CF5), 1% flaxseed (CF1), or 5% coconut oil (CS) for 24 wk. LDLrKO mice fed a cholesterol-supplemented diet exhibited a rise in plasma cholesterol without a change in triglycerides and an increase in atherosclerotic plaque formation. The CS mice exhibited elevated levels of plasma cholesterol, triglycerides, and saturated fatty acids and an increase in plaque development. Supplementation of the cholesterol-enriched diet with 10% (wt/wt) ground flaxseed lowered plasma cholesterol and saturated fatty acids, increased plasma ALA, and inhibited plaque formation in the aorta and aortic sinus compared with mice fed a diet supplemented with only dietary cholesterol. The expression of proliferating cell nuclear antigen (PCNA) and the inflammatory markers IL-6, mac-3, and VCAM-1 was increased in aortic tissue from CH and CS mice. This expression was significantly reduced or normalized when flaxseed was included in the diet. Our results demonstrate that dietary flaxseed can inhibit atherosclerosis in the LDLrKO mouse through a reduction of circulating cholesterol levels and, at a cellular level, via antiproliferative and anti-inflammatory actions. (Authors Abstract)